Late Phase 2 Study of DU-176b in Patients With Non-Valvular Atrial Fibrillation

This study has been completed.
Sponsor:
Information provided by:
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT00829933
First received: January 26, 2009
Last updated: NA
Last verified: January 2009
History: No changes posted
  Purpose

The primary objective of this study is to compare the incidence of hemorrhagic events in patients treated for non-valvular atrial fibrillation with DU-176b at each dose level versus warfarin potassium (warfarin). The secondary objective includes between-group comparisons with regard to incidence of thromboembolic events, pharmacodynamic parameters, and biomarkers for the efficacy evaluation, as well as incidence of adverse events and adverse reaction for the safety evaluation.


Condition Intervention Phase
Atrial Fibrillation
Drug: DU-176b tablets
Drug: Warfarin potassium tablets
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized Dose-Ranging Controlled Trial of DU-176b Versus Warfarin Potassium in Patients With Non-Valvular Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • Incidence of hemorrhagic events (major bleeding, clinically relevant non-major bleeding and minor bleeding ) identified during the period from the entry to the treatment period until completion or termination of the treatment. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of thromboembolic events (cerebral infarction and systemic embolism) identified during the period from the entry to the treatment period until completion or termination of the treatment. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events and adverse reactions identified during the period from the entry to the treatment period until completion or termination of the treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic parameters (PT, PT-INR, and APTT) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Plasma DU-176 concentration [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Pharmacodynamic biomarkers (F1+2, TAT, and D-dimer ) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 536
Study Start Date: March 2007
Study Completion Date: September 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
DU-176b low dose
Drug: DU-176b tablets
DU-176b tablets taken once daily for up to 12 weeks
Experimental: 2
DU-176b intermediate dose
Drug: DU-176b tablets
DU-176b tablets taken once daily for up to 12 weeks
Experimental: 3
DU-176b high dose
Drug: DU-176b tablets
DU-176b tablets taken once daily for up to 12 weeks
Active Comparator: 4
Warfarin
Drug: Warfarin potassium tablets
Warfarin potassium tablets taken once daily for up to 12 weeks

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with non-valvular atrial fibrillation who meet all of the following requirements will be considered for admission to the study:

    • Age≧20years
    • Atrial fibrillation confirmed by at least 2 electrocardiographic(ECG) tracings taken at an interval of ≧1week during the year before enrollment
  • Presence of any (at least )one of the following risk factors for embolism:

    • Hypertension
    • Diabetes mellitus
    • Congestive heart failure
    • Previous transient ischemic attack (TIA) or cerebral infarction (more than 30 days before giving informed consent )
    • Age≧75 years
    • At time of giving informed consent.
    • To be confirmed on ECG charts, etc.

Exclusion Criteria:

  • Presence of any of the following conditions with increased risk of hemorrhage:

    • History of intracranial, intraocular (excluding bleeding beneath the bulbar conjunctiva ), intrathecal, retroperitoneal, or non-traumatic intraarticular hemorrhage
    • History of gastrointestinal hemorrhage during the year before giving informed consent
    • History of peptic ulcers during the 90 days before giving informed consent
    • Surgical treatment or trauma requiring hospitalization during the 30 days before giving informed consent
    • Hemoglobin level <10 g/dL platelet count <10 ×10000 /μL at screening examinations
    • Active hemorrhage* present at giving informed consent or at enrollment
    • Any invasive therapeutic or diagnostic procedure (e.g., surgery, tissue, biopsy, and tooth extraction) scheduled during the period from the time of informed consent until completion of the trial treatment.
    • Any congenital hemorrhagic disease
  • History of cerebral infarction or TIA within 30 days before giving informed consent
  • Current treatment with any anticoagulant(other than warfarin)
  • Concurrent rheumatic valvular disease
  • History of valvular surgery
  • Concurrent infectious endocarditis
  • Concurrent cardiac myxoma
  • Confirmed left ventricular or left atrial thrombosis
  • Any congenital condition with a tendency toward thrombosis
  • Electrical or pharmacological defibrillation scheduled during the trial treatment
  • Uncontrolled hypertension (persistently high systolic [>160mmHg]or diastolic [>100mmHg] pressure)
  • Uncontrolled diabetes mellitus
  • Renal or hepatic dysfunction (as defined below ), confirmed at screening examinations

    • Serum creatinine>1.5mg/dL
    • AST(GOT)or ALT(GPT)≧twice the upper limit of the reference range
    • Total bilirubin ≧twice the upper limit of the reference range
  • Current antiplatelet therapy for any concomitant illness that may be aggravated after discontinuation of the therapy.
  • Any concurrent severe cardiac disease
  • Known allergy to warfarin or any condition contraindicating its use
  • Inability to discontinue current treatment with vitamin K
  • Confirmed or potential pregnancy, wish to become pregnant during the study period, or current breast feeding
  • Previous treatment with DU-176b
  • Participation in a trial of any other drug during the 6 month before giving informed consent
  • Any other condition that disqualifies the patient for the study in the opinion of the investigator/subinvestigator *This includes ecchymosis identified as at least one hematoma sized ≧5 cm in longer diameter, macroscopic hematuria, and microscopic hematuria defined as a ≧2+test or a 1+ test for occult blood with a urine sediment containing ≧10 red cells per high-power field (except for a 2+ occult blood test persisting for 1 year before giving informed consent).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00829933

Locations
Japan
Tokyo, Japan
Sponsors and Collaborators
Daiichi Sankyo Co., Ltd.
  More Information

No publications provided

Responsible Party: Clinical Development Department III, Group II, Daiichi Sankyo Co., Ltd.
ClinicalTrials.gov Identifier: NCT00829933     History of Changes
Other Study ID Numbers: DU176b-C-J225
Study First Received: January 26, 2009
Last Updated: January 26, 2009
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Daiichi Sankyo Inc.:
Atrial fibrillation
Factor Xa inhibition

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014